Dyskerin (FIG. 1) is a 58-kD nucleolar protein that is associated with the H/ACA box SnoRNAs, present in the small ribonucleoprotein particles in charge of pseudouridylation modification of ribosomal RNA. On the other hand, it is also a component of the telomerase complex, which is responsible for maintaining telomeric repetitions at the chromosome ends. The X-chromosome-linked form of dyskeratosis congenita (DC) (Marrone et al., 2003; Besseler et al., 2004) is a congenital syndrome that causes bone marrow failure and is associated with greater susceptibility to cancer. This form of dyskeratosis is caused by a specific mutation of the DKC1 gene, which encodes dyskerin. There also exists an autosomal dominant dyskeratosis congenita; in this case, the disease is associated with mutations in the RNA component of telomerase (hTR) (Heiss et al., 1998). In the fibroblasts and lymphoblasts of patients with dyskeratosis congenita there is less telomerase activity, and the telomeres are shorter than those of cells not affected by the disease (Siriniavin et al., 1975; Trowbridge et al., 1977). In the cells of patients with the X-chromosome-linked form of dyskeratosis congenita, telomerase defects have been overcome by expressing the reverse transcriptase catalytic subunit (hTERT) ectopically (Mitchell et al., 1999). In dyskeratosis congenita caused by mutations in hTR, the only way to recover telomerase activity is by re-expressing hTR (Fu et al., 2003).
Telomeres are composed of 500-2,000 repetitions of the TTAGGG conserved sequence at the chromosome 3′ end and their shortening through successive divisions becomes a limitation for the cell's proliferation capacity. Telomeres are susceptible to suffering DNA damage caused by exogenous agents, including cisplatin. It has been described that cisplatin is capable of inhibiting telomerase activity in different cell lines (Ishibashi et al., 1998; Burger et al., 1997). There are several hypotheses as to how this inhibition may occur. One possibility is the formation of G-Pt-G adducts, typical of cisplatin, in the repeated sequence of TTAGGG telomeres. Alternatively, interactions of cisplatin with sulfhydryl groups essential for the reverse transcriptase catalytic subunit (hTERT) and it could even be due to the reduction in hTERT expression (Burger et al., 1997).